The esters of 3-quinuclidinol, the structure of which is shown below, contain the functional groups of acetylcholine and are known to possess muscarinic and antimuscarinic activity. ##STR1## Biologically active quinuclidinol derivatives contain chiral centers, and so it is often highly desirable that they be in an enantiomerically-enriched or pure form, so as to improve specificity and reduce side effects. Consequently, the preparation of high optical purity quinuclidinols is of great interest.
The resolution of racemic mixtures of 3-quinuclidinol derivities has been reported. Rehavi et al., in 21 Life Sciences 1293 (1977), disclose the enzyme-catalyzed hydrolysis of (R)-3-quinuclidinol butyrate by butyrylcholine esterase from horse serum. However, the enantioselective hydrolysis of the (R)-ester to obtain R-alcohol was very slow (about 10 hours), resulted in low recovery and relatively low enantiomeric enrichment of the R-enantiomer, and required an enzyme which is very expensive.
There is still a need in the art for a simple, efficient, and inexpensive method of enantiomerically enriching chiral quinuclidinol and its derivatives. This need and others are met by the process of the present invention, which is summarized and described in detail below.